第四章 血浆脂蛋白及其代谢紊乱 plasma lipoproteins and its metabolic disorder

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第四章 血浆脂蛋白及其代谢紊乱 Plasma Lipoproteins and Its Me tabolic Disorder 湘南学院医学检验系 湘南学院医学检验系 临床生化检验教研室 临床生化检验教研室

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第四章 血浆脂蛋白及其代谢紊乱 Plasma Lipoproteins and Its Metabolic Disorder. 湘南学院医学检验系       临床生化检验教研室. 本章内容概要. 第一节 血浆脂蛋白结构与受体 第二节 脂蛋白代谢 第三节 脂蛋白代谢紊乱 第四节 脂蛋白代谢紊乱与 AS 第五节 血脂、脂蛋白及载脂蛋白测定. 教学目标. [ 掌握 ] 脂蛋白代谢紊乱(高脂血症分型及特征),血浆脂类及脂蛋白测定方法 。 [ 熟悉 ] 血浆脂蛋白的化学和正常代谢,载脂蛋白的结构与功能 。 [ 了解 ] 脂蛋白受体及代谢有关酶 。. - PowerPoint PPT Presentation

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  • Plasma Lipoproteins and Its Metabolic Disorder

  • AS

  • [] [] [] [] 6

  • 951. 2. 3. 4. 5. 6. 51. 2. 3.

  • (triglyceride, TG)

    (free cholesterol,FC)

    cholesterol ester, CE)

    (TC)

    (phospholipid, PL)

    (free fatty acid, FFA)

    () plasma lipids (glycolipid)

  • 1 +(TGPLFC+CE) (1) HDL>LDL>VLDL>CM CM>VLDL>LDL>HDL (2) (Apo)()

  • 2 ApoPL(PL) (TGCE)PL ApoPLFC Apo

  • , TGCE PLFFA

  • HDL LDL VLDL Lp(a) IDL

  • CM VLDL LDL HDL CM - LP-LP-LP

  • (ultra centrifugation method)(density-gradient method) Sf (Svedberg floatation rate)

    Sf

    d(g/ml)

    CM

    >400

  • (electrophoresis method)

  • TGrich LipoproteinChrich Lipoprotein

  • CM, , CM (), AS

  • VLDL

  • LDL,ASASLDL

  • HDL HDLAS,

  • () ()

  • ()(apolipoproteinApo) 12 1972AlaupovicApoABCDEFGHJ

  • apoAapoAapoAapoAapoAapoAapoAHDL

  • apoBapoB100apoB48apoB100LDLapoB48CM

  • apoCapoCapoCapoCapoCVLDLapoB100apoC apoD apoEapoE2apoE3apoE4

  • 3 LCATapoAapoAapoCapoALpLapoCapoAapoCHLapoA

  • apoBapoBELDLapoEapoBEapoELDLLRPapoAHDL

  • CETPHDLVLDLLDLPTPCMVLDLHDL apoDLCATapoAapoA-apoD-LCAT

  • () genotype ()(Phenotype)

  • 1

    ( 1 )ApoAApoBApo(a)

    (intron) 3

    (exon) 4

  • ( 2) ApoACA112 ApoECC193

  • 2 ( 1 ) ApoA 1 863bp34 658bp ApoAApoA 11

  • ( 2 ) ApoB 2ApoB100 43kb2829 7 572bp39bp

  • ( 3 ) ApoE 1934 ApoE3 ApoE2ApoE3ApoE4 E2/2E3/3()E4/46 E2/3E2/4E3/4 ( 4 ) ApoC ApoCApoC3347bp 3133bp3,4

  • ( 5 ) Apo(a) 6 525kb1918 Apo(a)2634

  • ApoCIApoA

  • *A 11q23-qApoAA1 q23-q23ApoAA11ApoA(a)6Apo(a)B2q24-q23ApoBC19q13.2ApoCC19ApoCC11ApoCD 3ApoDE19q13.2ApoEH 17q23-qApoHJ8p21CL

  • ApoEApoC ApoCII

    19q311q2 , , , ApoCApoAApoAApoA

  • LDLVLDL

  • LDLLDL receptor 1974 LDL 1LDL 836115kD5

  • 2LDL1 coated pit ;

  • (2) ApoB100ApoE ApoB-E ApoB48 LDLApoB100LDLLDL ApoB/ELDL

  • 3LDLLDL receptor pathway 1LDLApoB100EVLDL-VLDLLDLLDL-VLDLVLDL-LP CEApoApoEApoCVLDL

  • 2LDL LDL+LDL LDL-LDLcoated vesicles LDLLDLLDL Apo CE FFA+FC TG +FFA

  • (3) FC Ch HMGCoA ACATCoAFCCE LDLLDLLDL

  • 4 LDLLDL VLDL CM LDLCMCMApoB48LDLApoEApoCLDLCM

  • VLDL 1 LDL5 2 ApoEVLDL-VLDLApoB100LDL Ch

  • 3 VLDL-VLDL 4 1As 2

  • scavenger receptor LDL LDL LDL AsLDL-CELDLLDLLDLLDLLDL

  • 1

    220 ku,, LDLN-C-inside-out6N-C

  • 2 1LDL LDLLDLox-LDLAs 2

  • 3 LDLox-LDLAs LDL

  • HDL(RCT) VLDL-IDL-LDLVLDL, IDLLDL,CMChTGCMLP

  • (CM)

    TG TGTG :

  • CM

  • ()VLDL1.2.TG(50%-70%)ApoB100ChCM3.TG 4.

  • VLDLHDL IDL

  • VLDL TGVLDL

  • () LDL1.VLDL2. Ch(45%-50%)CEHDL(CETP) APOApoB100 3.4. (1) LDL

  • 2 LDLLDLLDLLDL (ox-LDL)(scavenger receptor, SR)LDL* 45%LDL2/3LDL1/3

  • LDL

  • LDL

  • LDL,LDLLDL

  • ()HDL 1. 2. 3. HDLApoEApoC HDLHDL 4.

  • HDL

  • HDLHDL3 HDL2 LCAT CETP

  • Hyperlipoproteinemia Hyperlipidemia TG/TC

  • :

  • ApoLP WHOab

  • ()CM 1. 1LPL 2ApoC Apo C() LPL CMTG CMCM CM 2.

  • 3.14CM 2TG 3CM 4CM 5LPLLPLApoC

  • ()IIa1. LDL (1) LDL (2) LDLLDL (3) LDL LDLLDL LDLLDL-Ch AS

  • 2. ASAS3.12 TG34LDL ApoB

  • () b-LP -LP 1.: ApoB100VLDLLDL 2. baLDL

  • 3. (1 2 TG 3LPPre LP 4 LDL VLDL

  • () (-VLDL-) 1. ApoE ApoEApoE2E3E4ApoE(VLDL)E2VLDLApoE3/E3VLDLApoE2/E2VLDLVLDL

  • 2.AS3.1 2TG Ch 3-VLDL LPPre LP--VLDL4 IDL (-VLDL)

  • () (TG VLDL) 1. VLDL/VLDL

  • 2.142 TG Ch 3 Pre 4 VLDL VLDL

  • 3.

  • () (CM-LP) 1. ApoC LPL CMVLDL TG LPL

  • 2. 203050

    3.12TG Ch 3CM 4CM VLDL

  • () HDL HDLASASHDLHDL 1 HDL-Ch> 2.6mmol/L0.78-2.2mmol/L0.3-0.85g/L

  • 2 (1) CETPCETPHDL-CEHDL, HDL HTGL, HDL, HDL HDL, HDL-ch(3~5) (2)

  • CETP HTGL HDL HDL-C2.6mmol/LHDL CETPHTGLHDL

    HDL

  • (secondary hyperlipoproteinemia) () , () () ()

  • VLDLLPLCMVLDLTG TG

  • ab: LPL,VLDL; HTGL,IDL; LDL,LDL

  • Cushing VLDLVLDLLDLa b

  • ApoBVLDLVLDLLDLb LPLVLDL

  • AS AS HDLAS

  • ASASLDL-VLDL oxLDLAS HDLAS AS

  • AS

  • CMVLDLLPLCMIDLApoE -VLDL(ApoE)-VLDLASAS

  • LDL LDLLDLLDL,LDL: LDL LDL LDL LDLApoB100LDLLDLAS

  • LDL-CAS LDLAB: B(LDL)AS,BLDL,LDLLDLCHD LDL(SD-LDL) BLDL

  • (a)LP-(a)Lipoprotein(a) 1963LDL

    TGPLFCCE ApoB100Apo(a)()

    LDL

  • LP(a)As,Apo(a)As

  • 1 2LDL 3 4 5 6 HDLAS

  • HDLApoAIApoB

  • HDL: CENCEHFCHDLNCEH FC: NCEH NCEH

  • ASAS

  • TCTGHDL-CLDL-C ApoAIApoBLpa TCTGHDL-CLDL-C 4 TCTG

  • CDC

  • 12h4

  • () (CEH)(cholesterol oxidaseCOD)4H2O2(POD) H2O24-(4AAP)(PAP)500nm

  • -4060001-2 C

  • 2.85.2mmolL

  • 112020405070234

  • 21TC - CoA 2TC

  • () -----GPO-PAP

    C

  • 0.55-1.70mmol/L 2.30mmol/L 4.50mmol/LTG

  • 1TG TGCHDTG 2TG

  • () .

  • ()---LDLVLDLLp(a)HDL(TC)HDL(HDL-C)HDLTGpH4h

  • HDL-C 0.9mmol/L

  • :(1)HDL-CHDL-C0.9mmolL(2)HDL-C(3)TGHDL-C4HDL-C5HDL-C6HDL-C

  • ()-----Friedewald

    LDL-CTCHDL-CTG2.2(mmolL) FriedewaldLDL-CTCTGHDL-CLDL-C CMTG>4.52mmolL(400mgd1)-FriedewaldLDL-C

  • LDL-C 2.13.1mmol/L 2.8mmol/L

  • : LDL(LDL-C)LDLLDL-CTCLDL-CLDL-CLDL-C

  • AIB ApoAIApoBApoAApoBApoAIApoBApoAIApoB

  • ApoAI1.00~1.50gLApoB0.80~1.00gL

  • ApoAIHDLHDLApoBLDLLDLLDLApoAIApoB,HDL-CLDL-CApoAIApoBApoAIApoB

  • 1 2ApoAAB100 C 3LDL??LDL??? 4CM VLDL LDL HDL 5? 6? 7APOA1APOB100HDLLDL

    1.063g/ml(1.75mol/L Nacl)1.063 1.063(HDL) Sf LDL VLDLLDL LDL VLDLLDL

    1 ApoB100/ApoE,ApoB100ApoELDLligand VLDLVLDL-VLDL2EGF 3 4 5 C- LDL,LDLLDL